DESCRIPTION (adapted from the application) Mary Waltner-Law received her Ph.D. from Purdue University in 1996 and has been a post-doctoral research fellow in the laboratory of Dr. Daryl Granner at the Vanderbilt University School of Medicine from 1996-present. Dr. Granner's laboratory studies the hormonal regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression and Dr. Waltner-Law has been studying the role of signal transduction pathways that mediate the repression of this gene in response to insulin. Dr. Waltner-Law has chosen to expand her research to study two factors, the transcription factor, NF-kappaB, and the corepressor, TLE1. Dr. Waltner-Law's immediate research goals include 1) determining how insulin regulates these factors and 2) identifying genes that are regulated by these factors in response to insulin. This grant will provide Dr. Waltner-Law with the additional mentored research experience necessary to achieve these goals. Information gained from the proposed experiments will enable her to fulfill her long-term goal of establishing independent research in her own laboratory to study the expression of genes encoding metabolic enzymes. By understanding how insulin regulates transcription factors and gene expression, she will be able to identify defective transcriptional processes in metabolic diseases, such as diabetes. Dr. Waltner-Law has proposed to use several techniques that are new to her, including mass spectrometry and perfusion studies in transgenic mice. She has access to the Mass Spectrometry Research Center at Vanderbilt University and will attend classes that will enable to her to identify post-translationally modified sites using mass spectrometry. The facilities and collaborative environment in the Department of Molecular Physiology and Biophysics will allow her to utilize the physiological techniques necessary to answer the questions proposed in this grant. Additionally, Dr. Waltner-Law will have access to the Diabetes Research and Training Center at Vanderbilt, which maintains a number of core labs designed to facilitate diabetes research. The techniques proposed in this grant will be invaluable for Dr. Waltner-Law to study the regulation of transcription and gene expression in the future.